Direct photocatalyzed hydrogen atom transfer (d-HAT) can be considered a method of choice for the elaboration of aliphatic C-H bonds. In this manifold, a photocatalyst (PCHAT) exploits the energy of a photon to trigger the homolytic cleavage of such bonds in organic compounds. Selective C-H bond elaboration may be achieved by a judicious choice of the hydrogen abstractor (key parameters are the electronic character and the molecular structure), as well as reaction additives. Different are the classes of PCsHAT available, including aromatic ketones, xanthene dyes (Eosin Y), polyoxometalates, uranyl salts, a metal-oxo porphyrin and a tris(amino)cyclopropenium radical dication. The processes (mainly C-C bond formation) are in most cases carried out under mild conditions with the help of visible light. The aim of this review is to offer a comprehensive survey of the synthetic applications of photocatalyzed d-HAT.

Direct Photocatalyzed Hydrogen Atom Transfer (HAT) for Aliphatic C-H Bonds Elaboration

In recent years, visible light-induced transition metal catalysis has emerged as a new paradigm in organic photocatalysis, which has led to the discovery of unprecedented transformations as well as the improvement of known reactions. In this subfield of photocatalysis, a transition metal complex serves a double duty by harvesting photon energy and then enabling bond forming/breaking events mostly via a single catalytic cycle, thus contrasting the established dual photocatalysis in which an exogenous photosensitizer is employed. In addition, this approach often synergistically combines catalyst-substrate interaction with photoinduced process, a feature that is uncommon in conventional photoredox chemistry. This Review describes the early development and recent advances of this emerging field.

Visible Light-Induced Transition Metal Catalysis.

The development of transition metal (TM) catalysis for organic synthesis under visible light without recourse to typical photoredox catalysts has become a rapidly growing area of research and has b...

Transition Metal-Catalyzed Organic Reactions under Visible Light: Recent Developments and Future Perspectives

Radical cascade reactions are an attractive tool for the rapid construction of complex molecular architectures. Although a large number of powerful radical cascades have been developed, stoichiometric amounts of reagents and/or additives are often required to mediate these processes. Radical relay strategies, in which radical character is recycled, require only a catalytic amount of reagent and are particularly attractive as they promise cascades that are high in atom economy. This tutorial review highlights recent advances in this rapidly developing area by setting out and dissecting the reaction designs underpinning state-of-the-art processes involving radical relays. Advances in the field of radical relay cascades will open the door to more efficient synthesis with far-reaching benefits for the makers and end-users of complex molecules.

Catalytic cascade reactions by radical relay

Transition metal catalyzed C-H activation has developed a contemporary approach to the omnipresent area of retrosynthetic disconnection. Scientific researchers have been tempted to take the help of this methodology to plan their synthetic discourses. This paradigm shift has helped in the development of industrial units as well, making the synthesis of natural products and pharmaceutical drugs step-economical. In the vast zone of C-H bond activation, the functionalization of proximal C-H bonds has gained utmost popularity. Unlike the activation of proximal C-H bonds, the distal C-H functionalization is more strenuous and requires distinctly specialized techniques. In this review, we have compiled various methods adopted to functionalize distal C-H bonds, mechanistic insights within each of these procedures, and the scope of the methodology. With this review, we give a complete overview of the expeditious progress the distal C-H activation has made in the field of synthetic organic chemistry while also highlighting its pitfalls, thus leaving the field open for further synthetic modifications.

Toolbox for Distal C-H Bond Functionalizations in Organic Molecules.

Selective functionalization of ubiquitous unactivated C–H bonds is a continuous quest for synthetic organic chemists. In addition to transition metal catalysis, which typically operates under a two-electron manifold, a recent renaissance in the radical approach relying on the hydrogen atom transfer (HAT) process has led to tremendous growth in the area. Despite several challenges, protocols proceeding via HAT are highly sought after as they allow for relatively easy activation of inert C–H bonds under mild conditions leading to a broader scope and higher functional group tolerance and sometimes complementary reactivity over methods relying on traditional transition metal catalysis. A number of methods operating via heteroatom-based HAT have been extensively reported over the past few years, while methods employing more challenging carbon analogues have been less explored. Recent developments of mild methodologies for generation of various carbon-centered radical species enabled their utilization in the HAT process, which, in turn, led to the development of remote C(sp3)–H functionalization reactions of alcohols, amines, amides and related compounds. This review covers mostly recent advances in C–H functionalization reactions involving the HAT step to carbon-centered radicals.

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C–H functionalization reactions enabled by hydrogen atom transfer to carbon-centered radicals

The Mizoroki-Heck reaction is one of the most efficient methods for alkenylation of aryl, vinyl, and alkyl halides. Given its innate nature, this protocol requires the employment of compounds possessing a halogen atom at the site of functionalization. However, the accessibility of organic molecules possessing a halogen atom at a particular site in aliphatic systems is extremely limited. Thus, a protocol that allows a Heck reaction to occur at a specific nonfunctionalized C(sp3 )-H site is desirable. Reported here is a radical relay Heck reaction which allows selective remote alkenylation of aliphatic alcohols at unactivated β-, γ-, and δ-C(sp3 )-H sites. The use of an easily installed/removed Si-based auxiliary enables selective I-atom/radical translocation events at remote C-H sites followed by the Heck reaction. Notably, the reaction proceeds smoothly under mild visible-light-mediated conditions at room temperature, producing highly modifiable and valuable alkenol products from readily available alcohols feedstocks.

Aliphatic Radical Relay Heck Reaction at Unactivated C(sp 3 )−H Sites of Alcohols

A mild visible-light-induced Pd-catalyzed intramolecular C-H arylation of amides is reported. The method operates by cleavage of a C(sp2 )-O bond, leading to hybrid aryl Pd-radical intermediates. The following 1,5-hydrogen atom translocation, intramolecular cyclization, and rearomatization steps lead to valuable oxindole and isoindoline-1-one motifs. Notably, this method provides access to products with readily enolizable functional groups that are incompatible with traditional Pd-catalyzed conditions.

Sumon Sarkar

Papers

Visible Light-Induced Transition Metal Catalysis.

C–H functionalization reactions enabled by hydrogen atom transfer to carbon-centered radicals

Aliphatic Radical Relay Heck Reaction at Unactivated C(sp 3 )−H Sites of Alcohols

Visible-Light-Induced Palladium-Catalyzed Generation of Aryl Radicals from Aryl Triflates